This P50 application is for the renewal of the Mayo SPORE In Brain Cancer for years 6-10. The SPORE will support a multidisciplinary team of basic and applied science investigators to perform translational research directed at significantly reducing morbidity and mortality from malignant gliomas. Brian Patrick O'Neill, M.D. will serve as Overall Principal Investigator and Director of the Administrative Core. Robert B. Jenkins, M.D., Ph.D. will serve as Overall Co-Principal Investigator and Administrative Core Co-Director. The translational research objectives of the SPORE will be directed by 14 investigators from 8 departments at Mayo Clinic in Rochester, all with a demonstrable history of collaborative and translational research. The SPORE comprises 4 Mayo investigator- initiated research projects and 4 scientific core resources consolidated by the Administrative Core. The SPORE also includes career development and developmental research programs. SPORE Research Projects 1. Influence of DNA repair on PARP inhibitor efficacy In GBM (Co-Leaders: J.N. Sarkaria, M.D., and N. Laack, M.D.) 2. Optimizing Measles Virotherapy In the Treatment of Gliomas (Co-Leaders: E. Galanis, M.D., D.Sc. and I.F. Parney, M.D., Ph.D.) 3. The Role of MMSET in DNA damage response and chemoradioresistance of glioblastoma (Co-Leaders: Z. Lou, Ph.D. and J. C. Buckner, M.D.) 4. Clinical Relevance of Chromosome 5p/9p/20q/8q Germline Alterations In Glioma (Co-Leaders: R. B. Jenkins, M.D., Ph.D and P. Yang, M.D., Ph.D. SPORE Scientific Cores A. Administrative Core (Director: B. P. O'Neill, M.D.; Co-Director: R.B. Jenkins, M.D., Ph.D.) B. Biostatistics Core (Director: K.V. Ballman, Ph.D.; Co-Director: W. Wu, Ph.D.) C. Pathology and Tissue Procurement Core (Director: C. Giannini, M.D., Ph.D.; Co-Director: F. Rodriguez, M.D.) D. Animal Core (Director: J.N. Sarkaria, M.D.; Co-Director: I.F. Parney, M.D., Ph.D.) E. Clinical Research Core (Director: J.C. Buckner, M.D.; Co-Director: D. H. Lachance, M.D.) Developmental Research Portfolio